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1.
Prev Med ; 186: 108088, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39084414

RESUMEN

BACKGROUND: Fatal opioid-related overdoses (OOD) continue to be a leading cause of preventable death across the US. Opioid Overdose Education and Naloxone Distribution programs (OENDs) play a vital role in addressing morbidity and mortality associated with opioid use, but access to such services is often inequitable. We utilized a geographic information system (GIS) and spatial analytical methods to inform prioritized placement of OEND services in Massachusetts. METHODS: We obtained addresses for OEND sites from the Massachusetts Department of Public Health and address-level fatal OOD data for January 2019 to December 2021 from the Massachusetts Registry of Vital Records and Statistics. Using location-allocation approaches in ArcGIS Pro, we created p-median models using locations of existing OEND sites and fatal OOD counts to identify areas that should be prioritized for future OEND placement. Variables included in our analysis were transportation mode, distance from public schools, race and ethnicity, and location feasibility. RESULTS: Three Massachusetts communities - Athol, Dorchester, and Fitchburg - were identified as priority sites for new OEND locations using location-allocation models based on capacity to maximize OOD prevention. Communities identified by the models for OEND placement had similar demographics and overdose rates (42.8 per 100,000 vs 40.1 per 100,000 population) to communities with existing OEND programs but lower naloxone kit distribution rates (2589 doses per 100,000 vs 3704 doses per 100,000). Further models demonstrated differential access based on location and transportation. CONCLUSION: Our analyses identified key areas of Massachusetts with greatest need for OEND services. Further, these results demonstrate the utility of using spatial epidemiological methods to inform public health recommendations.


Asunto(s)
Sistemas de Información Geográfica , Reducción del Daño , Naloxona , Antagonistas de Narcóticos , Humanos , Massachusetts , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Sobredosis de Opiáceos/prevención & control , Sobredosis de Opiáceos/epidemiología , Accesibilidad a los Servicios de Salud , Análisis Espacial , Sobredosis de Droga/prevención & control , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/epidemiología , Masculino
2.
Drug Alcohol Depend ; 251: 110947, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37666091

RESUMEN

BACKGROUND: Death certificate data provide powerful and sobering records of the opioid overdose crisis. In Massachusetts, where address-level decedent data are publicly available upon request, mapping and spatial analysis of fatal overdoses can provide valuable insights to inform prevention interventions. We describe how we used this approach to support a community-level intervention to reduce opioid-involved overdose mortality. METHODS: We developed a method to clean and geocode decedent data that substituted injury locations (the likely location of fatal overdoses) for deaths recorded in hospitals. After geomasking for greater privacy protection, we created maps to visualize the spatial distribution of decedent residence addresses, alone and juxtaposed with drive and walk-time distances to opioid treatment programs (OTPs), and place of death by overdose address. We used spatial statistical analyses to identify locations with significant clusters of overdoses. RESULTS: In the 8 intervention communities, 785 individuals died from opioid-involved overdoses between 2017 and 2020. We found that 19.7% of fatal overdoses were recorded in hospitals, 50.2% occurred at the decedent's residence, and 30.1% at another location. We identified overdose hotspots in study communities. By juxtaposing decedent residence data with drive- and walk-time analyses, we highlighted actionable spatial gaps in access to OTP treatment. CONCLUSION: To better understand local fatal opioid overdose risk environments and inform the development of community-level prevention interventions, we used publicly available address-level decedent data to conduct nuanced spatial analyses. Our approach can be replicated in other jurisdictions to inform overdose prevention responses.

3.
J Subst Abuse Treat ; 112: 42-48, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32199545

RESUMEN

BACKGROUND: Inpatient treatment for substance use disorders is a collection of strategies ranging from short term detoxification to longer term residential treatment. How those with opioid use disorder (OUD) navigate this inpatient treatment system after an encounter for detoxification and subsequent risk of opioid-related overdose is not well understood. METHODS: We used a comprehensive Massachusetts database to characterize the movement of people with OUD through inpatient care from 2013 to 2015, identifying admissions to inpatient detoxification, subsequent inpatient care, and opioid overdose while navigating treatment. We measured the person-years accumulated during each transition period to calculate rates of opioid-related overdose, and investigated how overdose differed in select populations. RESULTS: Sixty-one percent of inpatient detoxification admissions resulted in a subsequent inpatient detoxification admission without progressing to further inpatient care. Overall, there were 287 fatal and 7337 non-fatal overdoses. Persons exiting treatment after detoxification had the greatest risk of overdose (17.3 per 100 person-years) compared to those who exited after subsequent inpatient care (ranging from 5.9 to 6.6 overdoses per 100 person-years). Non-Hispanic whites were most at risk for opioid related overdose with 16 overdoses per 100 person-years and non-Hispanic blacks had the lowest risk with 5 overdoses per 100 person-years. CONCLUSIONS: The majority of inpatient detoxification admissions do not progress to further inpatient care. Recurrent inpatient detoxification admission is common, likely signifying relapse. Rather than functioning as the first step to inpatient care, inpatient detoxification might be more effective as a venue for implementing strategies to expand addiction services or treatment such as medications for opioid use disorder.


Asunto(s)
Sobredosis de Droga , Sobredosis de Opiáceos , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Sobredosis de Droga/tratamiento farmacológico , Humanos , Pacientes Internos , Massachusetts , Trastornos Relacionados con Opioides/tratamiento farmacológico
4.
Addiction ; 115(8): 1496-1508, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32096908

RESUMEN

BACKGROUND AND AIM: Medically managed opioid withdrawal (detox) can increase the risk of subsequent opioid overdose. We assessed the association between mortality following detox and receipt of medications for opioid use disorder (MOUD) and residential treatment after detox. DESIGN: Cohort study generated from individually linked public health data sets. SETTING: Massachusetts, USA. PARTICIPANTS: A total of 30 681 opioid detox patients with 61 819 detox episodes between 2012 and 2014. MEASUREMENTS: Treatment categories included no post-detox treatment, MOUD, residential treatment or both MOUD and residential treatment identified at monthly intervals. We classified treatment exposures in two ways: (a) 'on-treatment' included any month where a treatment was received and (b) 'with-discontinuation' individuals were considered exposed through the month following treatment discontinuation. We conducted multivariable Cox proportional hazards analyses and extended Kaplan-Meier estimator cumulative incidence for all-cause and opioid-related mortality for the treatment categories as monthly time-varying exposure variables. FINDINGS: Twelve months after detox, 41% received MOUD for a median of 3 months, 35% received residential treatment for a median of 2 months and 13% received both for a median of 5 months. In on-treatment analyses for all-cause mortality compared with no treatment, adjusted hazard ratios (AHR) were 0.34 [95% confidence interval (CI) = 0.27-0.43] for MOUD, 0.63 (95% CI = 0.47-0.84) for residential treatment and 0.11 (95% CI = 0.03-0.43) for both. In with-discontinuation analyses for all-cause mortality, compared with no treatment, AHRs were 0.52 (95% CI = 0.42-0.63) for MOUD, 0.76 (95% CI = 0.59-0.96) for residential treatment and 0.21 (95% CI = 0.08-0.55) for both. Results were similar for opioid-related overdose mortality. CONCLUSIONS: Among people who have undergone medically managed opioid withdrawal, receipt of medications for opioid use disorder, residential treatment or the combination of medications for opioid use disorder and residential treatment were associated with substantially reduced mortality compared with no treatment.


Asunto(s)
Trastornos Relacionados con Opioides/mortalidad , Tratamiento Domiciliario/estadística & datos numéricos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Adolescente , Adulto , Buprenorfina/uso terapéutico , Estudios de Cohortes , Sobredosis de Droga/mortalidad , Femenino , Humanos , Masculino , Massachusetts/epidemiología , Metadona/uso terapéutico , Persona de Mediana Edad , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto Joven
5.
J Pediatr ; 191: 69-75, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29050752

RESUMEN

OBJECTIVE: To determine the association of maternal substance use disorders (SUDs) during pregnancy with adverse neonatal outcomes and infant hospital re-admissions, observational stays, and emergency department utilization in the first year of life. STUDY DESIGN: We analyzed 2 linked statewide datasets from 2002 to 2010: the Massachusetts Pregnancy to Early Life Longitudinal data system and the Massachusetts Bureau of Substance Abuse Services Management Information System. Generalized estimating equations were used to assess the association of maternal SUDs and neonatal outcomes and infant hospital-based care in the first year of life, controlling for maternal and infant characteristics. RESULTS: Maternal SUDs increased from 19.4 per 1000 live births in 2003 to 31.1 per 1000 live births in 2009. In the adjusted analysis, exposed neonates were more likely to be born preterm (aOR 1.85; 95% CI 1.75-1.96) and low birthweight (aOR 1.94; 95% CI 1.80-2.09). After controlling for maternal characteristics and preterm birth, SUD-exposed neonates were more likely to have intrauterine growth restriction, cardiac, respiratory, neurologic, infectious, hematologic, and feeding/nutrition problems, prolonged hospital stay, and higher mortality (aOR range 1.26-3.80). Exposed infants were more likely to be rehospitalized (aOR 1.10; 95% CI 1.04-1.17) but less likely to have an observational stay (aOR 0.90; 95% CI 0.82-0.99) or use the emergency department (aOR 0.87; 95% CI 0.83-0.90) in the first year of life. CONCLUSIONS: Infants born to mothers with SUD are at higher risk for adverse health outcomes in the perinatal period and are also more likely to be rehospitalized in the first year of life.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Enfermedades del Recién Nacido/etiología , Readmisión del Paciente/estadística & datos numéricos , Complicaciones del Embarazo , Trastornos Relacionados con Sustancias , Bases de Datos Factuales , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/terapia , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Estudios Longitudinales , Masculino , Massachusetts , Embarazo , Factores de Riesgo
6.
MMWR Morb Mortal Wkly Rep ; 66(14): 382-386, 2017 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-28406883

RESUMEN

Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50-100 times the potency of morphine, increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) (4). To guide overdose prevention and response activities, in April 2016, the Massachusetts Department of Public Health and the Office of the Chief Medical Examiner collaborated with CDC to investigate the characteristics of fentanyl overdose in three Massachusetts counties with high opioid overdose death rates. In these counties, medical examiner charts of opioid overdose decedents who died during October 1, 2014-March 31, 2015 were reviewed, and during April 2016, interviews were conducted with persons who used illicit opioids and witnessed or experienced an opioid overdose. Approximately two thirds of opioid overdose decedents tested positive for fentanyl on postmortem toxicology. Evidence for rapid progression of fentanyl overdose was common among both fatal and nonfatal overdoses. A majority of interview respondents reported successfully using multiple doses of naloxone, the antidote to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and enhancing existing opioid overdose education and prevention programs to include fentanyl-specific messaging and practices could help public health authorities mitigate adverse effects associated with overdoses, especially in communities affected by IMF.


Asunto(s)
Sobredosis de Droga/epidemiología , Fentanilo/envenenamiento , Adolescente , Adulto , Distribución por Edad , Analgésicos Opioides/envenenamiento , Sobredosis de Droga/etnología , Sobredosis de Droga/mortalidad , Sobredosis de Droga/prevención & control , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Drogas Ilícitas/legislación & jurisprudencia , Drogas Ilícitas/envenenamiento , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Naloxona/uso terapéutico , Factores de Riesgo , Distribución por Sexo , Población Blanca/estadística & datos numéricos , Adulto Joven
7.
Matern Child Health J ; 21(4): 893-902, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27832443

RESUMEN

Objectives Despite widely-known negative effects of substance use disorders (SUD) on women, children, and society, knowledge about population-based prevalence and impact of SUD and SUD treatment during the perinatal period is limited. Methods Population-based data from 375,851 singleton deliveries in Massachusetts 2003-2007 were drawn from a maternal-infant longitudinally-linked statewide dataset of vital statistics, hospital discharges (including emergency department (ED) visits), and SUD treatment records. Maternal SUD and SUD treatment were identified from 1-year pre-conception through delivery. We determined (1) the prevalence of SUD and SUD treatment; (2) the association of SUD with women's perinatal health service utilization, obstetric experiences, and birth outcomes; and (3) the association of SUD treatment with birth outcomes, using both bivariate and adjusted analyses. Results 5.5% of Massachusetts's deliveries between 2003 and 2007 occurred in mothers with SUD, but only 66% of them received SUD treatment pre-delivery. Women with SUD were poorer, less educated and had more health problems; utilized less prenatal care but more antenatal ED visits and hospitalizations, and had worse obstetric and birth outcomes. In adjusted analyses, SUD was associated with higher risk of prematurity (AOR 1.35, 95% CI 1.28-1.41) and low birth weight (LBW) (AOR 1.73, 95% CI 1.64-1.82). Women receiving SUD treatment had lower odds of prematurity (AOR 0.61, 95% CI 0.55-0.68) and LBW (AOR 0.54, 95% CI 0.49-0.61). Conclusions for Practice SUD treatment may improve perinatal outcomes among pregnant women with SUD, but many who need treatment don't receive it. Longitudinally-linked existing public health and programmatic records provide opportunities for states to monitor SUD identification and treatment.


Asunto(s)
Enfermedades del Recién Nacido/etiología , Atención Perinatal/estadística & datos numéricos , Complicaciones del Embarazo/etiología , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Estudios Longitudinales , Masculino , Massachusetts/epidemiología , Embarazo , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo , Prevalencia , Factores de Riesgo , Trastornos Relacionados con Sustancias/epidemiología
8.
Matern Child Health J ; 19(10): 2168-78, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25680703

RESUMEN

Substance use disorder (SUD) in women of reproductive age is associated with adverse health consequences for both women and their offspring. US states need a feasible population-based, case-identification tool to generate better approximations of SUD prevalence, treatment use, and treatment outcomes among women. This article presents the development of the Explicit Mention Substance Abuse Need for Treatment in Women (EMSANT-W), a gender-tailored tool based upon existing International Classification of Diseases, 9th Edition, Clinical Modification diagnostic code-based groupers that can be applied to hospital administrative data. Gender-tailoring entailed the addition of codes related to infants, pregnancy, and prescription drug abuse, as well as the creation of inclusion/exclusion rules based on other conditions present in the diagnostic record. Among 1,728,027 women and associated infants who accessed hospital care from January 1, 2002 to December 31, 2008 in Massachusetts, EMSANT-W identified 103,059 women with probable SUD. EMSANT-W identified 4,116 women who were not identified by the widely used Clinical Classifications Software for Mental Health and Substance Abuse (CCS-MHSA) and did not capture 853 women identified by CCS-MHSA. Content and approach innovations in EMSANT-W address potential limitations of the Clinical Classifications Software, and create a methodologically sound, gender-tailored and feasible population-based tool for identifying women of reproductive age in need of further evaluation for SUD treatment. Rapid changes in health care service infrastructure, delivery systems and policies require tools such as the EMSANT-W that provide more precise identification methods for sub-populations and can serve as the foundation for analyses of treatment use and outcomes.


Asunto(s)
Algoritmos , Hospitalización/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Femenino , Humanos , Prevalencia , Estados Unidos/epidemiología
9.
Drug Alcohol Depend ; 147: 151-9, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25496707

RESUMEN

INTRODUCTION: Longitudinal patterns of treatment utilization and relapse among women of reproductive age with substance use disorder (SUD) are not well known. In this statewide report spanning seven years we describe SUD prevalence, SUD treatment utilization, and differences in subsequent emergency department (ED) use and post-treatment relapse rates by type of treatment: none, 'acute only' (detoxification/stabilization), or 'ongoing' services. METHODS: We linked a statewide dataset of hospital discharge, observation stay and ED records with SUD treatment admission records from hospitals and freestanding facilities, and birth/fetal death certificates, in Massachusetts, 2002-2008. We aggregated episodes into individual woman records, identified evidence of SUD and treatment, and tested post-treatment outcomes. RESULTS: Nearly 150,000 (8.5%) of 1.7 million Massachusetts women aged 15-49 were identified as SUD-positive. Nearly half of SUD-positive women (71,533 or 48.3%) had evidence of hospital or facility-based SUD treatment; among these, 12% received acute care/detoxification only while 88% obtained 'ongoing' treatment. Treatment varied by substance type; women with dual diagnosis and those with opiate use were least likely to receive 'ongoing' treatment. Treated women were older and less likely to have a psychiatric history or chronic illness. Women who received 'acute only' services were more likely to relapse (12.4% vs. 9.6%) and had a 10% higher rate of ED visits post-treatment than women receiving 'ongoing' treatment. CONCLUSIONS: Many Massachusetts women of reproductive age need but do not receive adequate SUD treatment. 'Ongoing' services beyond detoxification/stabilization may reduce the likelihood of post-treatment relapse and/or reliance on the ED for subsequent medical care.


Asunto(s)
Trastornos Relacionados con Sustancias/rehabilitación , Adolescente , Adulto , Diagnóstico Dual (Psiquiatría) , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Recursos en Salud/estadística & datos numéricos , Humanos , Incidencia , Massachusetts/epidemiología , Trastornos Mentales/complicaciones , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Población , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/epidemiología , Resultado del Tratamiento , Adulto Joven
10.
Acad Emerg Med ; 21(12): 1459-68, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25491709

RESUMEN

OBJECTIVES: Substance use disorder (SUD) among women of reproductive age is a complex public health problem affecting a diverse spectrum of women and their families, with potential consequences across generations. The goals of this study were 1) to describe and compare the prevalence of patterns of injury requiring emergency department (ED) visits among SUD-positive and SUD-negative women and 2) among SUD-positive women, to investigate the association of specific categories of injury with type of substance used. METHODS: This study was a secondary analysis of a large, multisource health care utilization data set developed to analyze SUD prevalence, and health and substance abuse treatment outcomes, for women of reproductive age in Massachusetts, 2002 through 2008. Sources for this linked data set included diagnostic codes for ED, inpatient, and outpatient stay discharges; SUD facility treatment records; and vital records for women and for their neonates. RESULTS: Injury data (ICD-9-CM E-codes) were available for 127,227 SUD-positive women. Almost two-thirds of SUD-positive women had any type of injury, compared to 44.8% of SUD-negative women. The mean (±SD) number of events also differed (2.27 ± 4.1 for SUD-positive women vs. 0.73 ± 1.3 for SUD-negative women, p < 0.0001). For four specific injury types, the proportion injured was almost double for SUD-positive women (49.3% vs 23.4%), and the mean (±SD) number of events was more than double (0.72 ± 0.9 vs. 0.26 ± 0.5, p < 0.0001). The numbers and proportions of motor vehicle incidents and falls were significantly higher in SUD-positive women (22.5% vs. 12.5% and 26.6% vs. 11.0%, respectively), but the greatest differences were in self-inflicted injury (11.5% vs. 0.8%; mean ± SD events = 0.19 ± 0.9 vs. 0.009 ± 0.2, p < 0.0001) and purposefully inflicted injury (11.5% vs 1.9%, mean ± SD events = 0.18 ± 0.1 vs. 0.02 ± 0.2, p < 0.0001). In each of the injury categories that we examined, injury rates among SUD-positive women were lowest for alcohol disorders only and highest for alcohol and drug disorders combined. Among 33,600 women identified as using opioids, 2,132 (6.3%) presented to the ED with overdose. Multiple overdose visits were common (mean ± SD = 3.67 ± 6.70 visits). After adjustment for sociodemographic characteristics, psychiatric history, and complex/chronic illness, SUD remained a significant risk factor for all types of injury, but for the suicide/self-inflicted injury category, psychiatric history was by far the stronger predictor. CONCLUSIONS: The presence of SUD increases the likelihood that women in the 15- to 49-year age group will present to the ED with injury. Conversely, women with injury may be more likely to be involved in alcohol abuse or other substance use. The high rates of injury that we identified among women with SUD suggest the utility of including a brief, validated screen for substance use as part of an ED injury treatment protocol and referring injured women for assessment and/or treatment when scores indicate the likelihood of SUD.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Heridas y Lesiones/epidemiología , Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Adulto , Alcoholismo/epidemiología , Femenino , Humanos , Massachusetts , Persona de Mediana Edad , Aceptación de la Atención de Salud , Prevalencia , Factores de Riesgo , Suicidio/estadística & datos numéricos , Salud de la Mujer , Heridas y Lesiones/etiología , Adulto Joven
11.
J Subst Abuse Treat ; 47(2): 130-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24912862

RESUMEN

Administrative data from five states were used to examine whether continuity of specialty substance abuse treatment after detoxification predicts outcomes. We examined the influence of a 14-day continuity of care process measure on readmissions. Across multiple states, there was support that clients who received treatment for substance use disorders within 14-days after discharge from detoxification were less likely to be readmitted to detoxification. This was particularly true for reducing readmissions to another detoxification that was not followed with treatment and when continuity of care was in residential treatment. Continuity of care in outpatient treatment was related to a reduction in readmissions in some states, but not as often as when continuity of care occurred in residential treatment. A performance measure for continuity of care after detoxification is a useful tool to help providers monitor quality of care delivered and to alert them when improvement is needed.


Asunto(s)
Atención Ambulatoria/organización & administración , Continuidad de la Atención al Paciente/organización & administración , Readmisión del Paciente/estadística & datos numéricos , Trastornos Relacionados con Sustancias/rehabilitación , Adolescente , Adulto , Atención Ambulatoria/normas , Continuidad de la Atención al Paciente/normas , Atención a la Salud/organización & administración , Atención a la Salud/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de la Atención de Salud , Tratamiento Domiciliario/métodos , Centros de Tratamiento de Abuso de Sustancias , Resultado del Tratamiento , Adulto Joven
12.
J Cell Physiol ; 203(1): 111-7, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15368541

RESUMEN

The deposition of insoluble functional collagen occurs following extracellular proteolytic processing of procollagens by procollagen N- and C-proteinases, fibril formation, and lysyl oxidase dependent cross-linking. Procollagen C-proteinases in addition process and activate lysyl oxidase. The present study evaluates a possible role for procollagen C-proteinases in controlling different aspects of collagen deposition in vitro. Studies determine whether inhibition of procollagen C-proteinase activity with a specific BMP-1 inhibitor results in perturbations in lysyl oxidase activation, and in collagen processing, deposition, and cross-linking in phenotypically normal cultured murine MC3T3-E1 cells. Data show that BMP-1 Inhibitor dose dependently inhibits lysyl oxidase activation by up to 50% in undifferentiated proliferating cells. In differentiating cultures, BMP-1 inhibitor decreased collagen processing but did not inhibit the accumulation of mature collagen cross-links. Finally, electron microscopy studies show that collagen fibril diameter increased. Thus, inhibition of procollagen C-proteinases results in perturbed collagen deposition primarily via decreased collagen processing.


Asunto(s)
Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas Morfogenéticas Óseas/metabolismo , Colágeno Tipo I/metabolismo , Metaloendopeptidasas/antagonistas & inhibidores , Metaloendopeptidasas/metabolismo , Osteoblastos/enzimología , Proteína-Lisina 6-Oxidasa/metabolismo , Animales , Proteína Morfogenética Ósea 1 , Diferenciación Celular , División Celular , Células Cultivadas , Reactivos de Enlaces Cruzados/metabolismo , Interacciones Farmacológicas , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/farmacología , Ratones , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Procesamiento Proteico-Postraduccional , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta1
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